The principal objective of this research is to determine why tumor cells (HeLa) are resistant to glucocorticoids at particular stages of the cell cycle and responsive at others. Using synchronized populations of HeLa cells we will assess the influence of glucocorticoids on the progression of cells through the cell cycle. Studies are proposed to ascertain the time periods within the cell cycle when HeLa cells are resistant and responsive to glucocorticoids with regard to RNA and protein metabolism. We will determine when during the cell cycle steroid-receptor biosynthesis occurs and how glucocorticoids affect the biosynthesis and functions of their own receptors. We will quantitate and characterize the interaction of dexamethasone receptor complexes with nuclear acceptors as a function of the cell cycle. Studies are proposed to determine if dexamethasone-receptor complexes bind to metaphase mitosis chromosomes in a specific manner. These studies provide an appropriate rationale for in vivo synchronization of malignancies which will allow for drug treatment at most susceptible phases of the cell cycle.